Libster 2020.

Study characteristics
Methods	Trial design: RCT, double‐blinded Type of publication: journal publication  Setting: outpatient (elderly population) Recruitment dates:  4 June 2020 and 25 October 2020 Country: Argentina Language: English Number of centres: 11 Trial registration number: NCT04479163  Date of registration: 21 July 2020
Participants	Age: 77.1 (SD 8.6) years Sex: 37.5% of males in the intervention and control group together Ethnicity: NR Number of participants (recruited/allocated/evaluated): 165/160 (80 CP, 80 standard treatment)/160 Severity of condition according to study definition: mild signs and symptoms for < 48 hours at the time of screening for SARS‐CoV‐2 by reverse transcriptase polymerase chain reaction (RT‐PCR) Severity of condition according to WHO score: level 4‐6 Comorbidities: arterial hypertension, diabetes, obesity, chronic obstructive pulmonary disease, heart disease, chronic kidney disease, asthma or other respiratory disease, Non‐cirrhotic liver disease, cancer (not active), Neurologic disease Inclusion criteria Subjects ≥ 75 years of age irrespective of presenting comorbidities or between 65‐74 years of age with at least one comorbidity (hypertension or diabetes under pharmacologic treatment, obesity, chronic renal failure, cardiovascular disease, and COPD) Subjects had experienced at least one of each in the following two categories of signs and symptoms for < 48 hours at the time of screening for SARS‐CoV‐2 by RT‐PCR: temperature ≥ 37.5° C and/or unexplained sweating and/or chills dry cough, dyspnoea, fatigue, myalgia, anorexia, sore throat, dysgeusia, anosmia, and/or rhinorrhoea Confirmed diagnosis SARS‐CoV‐2 by RT‐PCR Give informed consent Exclusion criteria Severe respiratory disease Cardiac insufficiency Chronic renal failure Primary hypogammaglobulinaemias Myelodysplastic syndromes Chronic lymphoproliferative syndromes Monoclonal gammapathies Known hypersensitivity Active cancer HIV, HBV or HCV infection Chronic administration of immunosuppressants Body transplant history Chronic liver disease, Chronic lung disease with oxygen requirement Previous treatments (e.g. experimental drug therapies, oxygen therapy, ventilation): NR Donor eligibility criteria Infected with SARS‐CoV‐2 for a minimum of 10 days Asymptomatic for ≥ 3 days, and with two negative RT‐PCR tests Donor exclusion criteria: NR
Interventions	CP therapy or hyperimmune immunoglobulin therapy: CP therapy Details of CP Type of plasma: plasmaphaeresis Volume: 250 mL Number of doses: 1 Antibody test and antibody‐titre: IgG titre against SARS‐CoV‐2 spike (S) protein > 1:1000 (COVIDAR IgG, Instituto Leloir, Argentina)  Pathogen inactivated or not: NR RT‐PCR tested: NR Details of donors Sex: both  HLA and HNA antibody‐negative: NR Severity of disease: NR Timing from recovery from disease: infected with SARS‐CoV‐2 for a minimum of 10 days, asymptomatic for ≥ 3 days RT‐PCR tested: two negative RT‐PCR tests Treatment details, including time of plasma therapy (e.g. early stage of disease): early stage within 72 hours of mild COVID‐19 symptoms. For studies including a control group: comparator (type): placebo Concomitant therapy: NR Duration of follow‐up: 25 days  Treatment cross‐overs: none Compliance with assigned treatment: one subject voluntarily abandoned the trial on day 11 of follow‐up.
Outcomes	Primary study outcome(s): development of severe respiratory disease defined as a respiratory rate (RR) ≥ 30 and/or an O2 sat < 93% when breathing room air determined between 12 h after infusion of the investigational product (IP) and day 15 of study participation Primary review outcomes (outpatient) All‐cause mortality: yes reported (after 25 days follow‐up) Admission to hospital: NR Secondary review outcomes (outpatient) Number of participants with grade 1 and grade 2 AEs, including potential relationship between intervention and adverse reaction (e.g. TRALI, transfusion‐transmitted infection, TACO, TAD, acute transfusion reactions): NR Number of participants with grade 3 and grade 4 AEs, including potential relationship between intervention and adverse reaction (e.g. TRALI, transfusion‐transmitted infection, TACO, TAD, acute transfusion reactions): NR Number of participants with SAEs: yes for transfusion related events Development of clinical COVID‐19 symptoms, assessed with the WHO Clinical Progression Scale (WHO 2020f) up to longest follow‐up: NR Time to symptom onset: NR Clinical status, assessed by need for respiratory support with standardised scales (e.g. WHO Clinical Progression Scale (WHO 2020e), WHO Ordinal Scale for Clinical Improvement (WHO 2020f)) at up to 7 days, 8 to 15 days, 16 to 30 days: NR Mortality (time to event): NR 90‐day mortality: NR Length of hospital stay, for hospitalised patients: NR Admission on the ICU: NR Viral clearance, assessed with reverse transcription polymerase chain reaction (RT‐PCR) test for SARS‐CoV‐2 at baseline, up to 3, 7, and 15 days: NR QoL: NR Additional study outcomes Life‐threatening respiratory disease, defined as: need for 100% oxygen supplementation and/or non‐invasive ventilation and/or admission to ICU and/or Mechanical ventilation Critical systemic illness, defined as respiratory failure (PaO2/FiO2 ≤ 200 mmHg) and/or shock and/or multi‐organic distress syndrome (defined in supplementary material) Death associated with COVID‐19 (On 22 July 2020, we amended the protocol to include a fourth secondary endpoint including any of the three endpoints described above, alone or in combination) The distribution of serum titres 24 h after infusion in plasma versus placebo recipients
Notes	Preprint publication: 21 November 2020 Sponsor/funding: funded by The Bill and Melinda Gates Foundation and The Fundación INFANT Pandemic Fund. Registered in the Dirección de Sangre y Medicina Transfusional del Ministerio de Salud (PAEPCC19), Plataforma PRIISA (1421), and clinicaltrials.gov (NCT04479163). COIs: RL, GPM, DW and FPP are investigators in a phase 3 SARS CoV2 trial from Pfizer; no other relationships or activities that could appear to have influenced the submitted work. Other: early termination due to slow enrolment pace (enrolled 76% of the target population)